MeiraGTx Holdings Plc, a vertically integrated, clinical stage gene therapy company, today announced that it has acquired Vector Neurosciences Inc. in an all-stock transaction. As a result of the acquisition, which was signed and closed October 5, 2018, MeiraGTx has expanded its portfolio of clinical stage product candidates to include adeno-associated virus encoding glutamic acid decarboxylase, a gene therapy product candidate ready for continued Phase 2 clinical development for Parkinson’s disease. A prior Phase 2 clinical trial of AAV-GAD was completed and was the first successful randomized, double-blind, sham-controlled trial of its kind for a gene therapy product candidate targeting a brain disorder.
“This strategic acquisition gives us an exciting mid-stage product candidate with promising, sham-controlled clinical data and expands our portfolio of potential therapies for neurodegenerative diseases,” said Alexandria Forbes, Ph.D., president and chief executive officer of MeiraGTx. “We are excited to continue moving AAV-GAD through clinical development and look forward to potentially offering a novel therapy to patients with Parkinson’s disease.”
“With demonstrated expertise in gene therapy clinical development and manufacturing, we are very pleased to work with the talented team at MeiraGTx to continue the development of this novel gene therapy product candidate. AAV-GAD has the potential to transform the treatment of Parkinson’s disease patients, providing hope for patients with limited treatment options,” said Michael Kaplitt, M.D., Ph.D., co-founder of Vector.
About the AAV-GAD Phase 2 Clinical Results
In a blinded Phase 2 clinical trial of AAV-GAD in patients with medically refractory Parkinson’s disease, 45 patients were randomized 1:1 to receive either AAV-GAD gene therapy delivered by injection into the subthalamic nucleus on both sides of the brain or bilateral sham surgery. Subjects were followed for one year and all results remained blinded until the final treated patient reached the 6-month primary endpoint. The trial met the pre-specified, per-protocol primary endpoint, with a significant improvement in the off-medication motor section of the Unified Parkinson’s Disease Rating Scale part 3 compared to baseline. There was also a significant difference in the degree of improvement compared with patients in the sham arm. Other endpoints also showed significant improvements in AAV-GAD treated patients compared to patients in the sham arm.
- The primary outcome measure was the 6-month change from baseline in double-blind assessment of off-medication UPDRS motor scores.
- At the 6-month endpoint, UPDRS score for the AAV-GAD group decreased by 8.1 points (SD 1.7, 23.1%; p<0.0001) and by 4.7 points in the sham group (1.5, 12.7%; p=0.003).
- The AAV-GAD group showed a signi?cantly greater improvement from baseline in UPDRS scores compared with the sham group over the 6-month course of the study (RMANOVA, p=0.04).
- Significant difference in the response rate between groups, with responders being defined as patients achieving a 9-point or more improvement in UPDRS, which may be deemed clinically meaningful.
- At six months, 50% of AAV-GAD treated patients were responders compared with only 14% of patients in the sham arm.
- At 12 months, response rates were 63% and 24%, in AAV-GAD and sham arms respectively.
- A significant improvement in complications of medical therapy as measured by the UPDRS part 4 was observed in the AAV-GAD group at both six and 12 months, and not in patients in the sham arm at either time point.
- A significant decline in duration of disabling dyskinesia was observed only in the AAV-GAD treated patients.
- A significantly greater number of AAV-GAD treated patients showed more than one hour increase in the time spent in a good condition on medication compared with patients in the sham arm.
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AAV-GAD was well-tolerated, with no significant adverse events related to the therapy and no speech or cognitive complications were observed. The most commonly reported adverse events were transient mild or moderate headache (7 in treated arm vs. 2 in sham arm), nausea and worsening of Parkinson’s disease. The results of the trial were published in the March 2011 issue of The Lancet Neurology, the August 2014 issue of Journal of Clinical Investigation and the April 2017 issue of JCI Insight, building upon publications of the Phase 1 trial data in The Lancet and the Proceedings of the National Academy of Sciences.
In addition to these positive clinical outcomes, flurodeoxyglucose positron emission tomography analyses provided objective biological confirmation of improvements in abnormal brain networks associated with Parkinson’s disease following AAV-GAD gene therapy. These results were observed in patients treated in both Phase 1 and Phase 2 studies. Blinded analyses demonstrated significant improvements in abnormal thalamic metabolism, a key node in the movement circuitry, in the AAV-GAD treated patients. This pattern of brain network activity was not seen in untreated hemispheres or patients in the sham arm. Furthermore, a specific pattern of brain network activity was identified in those subjects with clinical improvements in the sham arm which was different from the pattern observed in AAV-GAD responders.
About AAV-GAD
AAV-GAD is an investigational gene therapy medicine designed to deliver the glutamic acid decarboxylase gene to the subthalamic nucleus in order to increase production of GABA, the primary inhibitory neurotransmitter in the human brain. GAD is the rate-limiting enzyme in the synthesis of GABA, therefore it is believed that increasing subthalamic nucleus GAD expression through gene therapy will result in normalization of motor circuits and improve symptoms in Parkinson’s disease patients without affecting other brain regions that can be responsible for complications of existing therapies. AAV-GAD has received Fast Track designation from the United Stated Food and Drug Administration.
Date: October 15, 2018
Source: nbc2
